Biosensor with rf signal transmission

ABSTRACT

A device ( 1 ) and method for measuring and or detecting the presence of biomolecules. The device comprises a resonance circuit arranged to operate and emit a resonance frequency (f). The resonance circuit comprises or is coupled to a sensor element ( 5 ) for detecting the binding of biomolecules ( 6   a ) to binding sites ( 5   a ). The binding of the biomolecules changes a physical property (R, L, C. mass) of the sensor element ( 5 ), which in it&#39;s turn, either directly when the sensor element forms part of the resonance circuit, or via a coupling of the sensor element to the resonance circuit, the resonance frequency. The change in the resonance frequency is detected. The device comprises a remote power transmission element, such as a photodiode or coil, for providing power to the resonance circuit using light or RF radiation respectively.

BACKGROUND OF THE INVENTION

This invention relates to a device comprising a sensor element havingbiomolecular binding sites for a biomolecule and a method for detectingbiomolecules in samples using such a device. Such devices are sometimesalso called biosensors cartridges, the sensor elements are sometimescalled biosensors. Biochips, biosensor chips, biological microchips,gene-chips or DNA chips are other words used to described such devicesor sensors. In such a device a signal is caused by an interaction of thebinding sites on a sensor surface with biochemical components in afluid. Typically a fluid component binds specifically to moleculesforming the bonding sites on a surface of the sensor element. Theinvention also relates to a method for determining the presence of orfor measuring the amount of biomolecules using a biosensor device.

Biosensors have been used to determine the presence and/or theconcentration of biomolecules in fluids. Examples of biomolecules areproteins, peptides, nucleic acids, carbohydrates and lipids. Examples offluids are simple buffers and biological fluids, such as blood, serum,plasma, saliva, urine, tissue homogenates. The to be determinedmolecules are often also called the analyte.

In a biosensor cartridge a sensor element is provided with bondingsites. To facilitate detection, often markers or labels are used, e.g.small beads, nanoparticles or special molecules with fluorescent ormagnetic properties. Labels can be attached before the analyte binds tothe sensor, but also thereafter. Microparticles are sometimes used as asolid phase to capture the analyte. Solid phase microparticles can bemade of a variety of materials, such as glass, plastic or latex,depending on the particular application. Some solid phase particles aremade of ferromagnetic materials to facilitate their separation fromcomplex suspensions or mixtures. The occurrence of a binding reaction,binding the solid phase microparticles (or some other marker which hascaptured the analyte) can be detected, e.g. by fluorescent markers.

The sensing of the molecules in the sensor element is called assay. Suchassays may have various formats, e.g. simple binding, sandwich assay,competitive assay, displacement assay. In conventional solid-phaseassays, the solid phase mainly aids in separating biomolecules that bindto the solid phase from molecules that do not bind to the solid phase.Separation can be facilitated by gravity, centrifugation, filtration,magnetism, flow-cytometry, microfluidics, etc. The separation may beperformed either in a single step in the assay or, more often, inmultiple steps.

Often, it is desirable to perform two or more different assays on thesame sample, in a single vessel and at about the same time. Such assaysare known in the art as multiplex assays. Multiplex assays are performedto determine simultaneously the presence or concentration of more thanone molecule in the sample being analyzed, or alternatively, to evaluateseveral characteristics of a single molecule, such as, the presence ofseveral epitopes on a single protein molecule.

Biosensors are meant to be tools for doctors or laboratory personnel.Measurement of a specific chemical reaction in the biosensor will leadto data that are to be interpreted by a certain apparatus. Due to thestrict rules in the medical world the biosensor will be used only once.In other words: it must be cheap and simple. And, as with all things tobe used in practice, operation is preferably easy.

An example of a device comprising a biosensor that can be relativelyeasily operated, is known from U.S. Pat. No. 6,376,187. This devicecomprises an identification chip, that is powered by light and of whichthe memory is read out inductively. Independent thereof, the cartridgecontains a biosensor, that is read out by means of fluorescence, i.e. afluorescent marker binds with the analyte, which in its term binds at abonding site and the presence of the flourescent marker at the bondingsite, i.e. on the sensor element is detected by means of fluorescence,i.e. a fluorescent signal.

It is however a disadvantage of the known biosensor cartridge, that thesensitivity and correctness of the output is dependent on the strengthof the fluorescent signal. Thus, if an intermediate medium distorts thesignal from the biosensor, the resulting measurement contains mistakes.And vice versa: if there is an output, it can only be trusted to alimited extent, since it contains an unknown, hardly or not controllablemistake due to the loss of intensity during the transfer of the signalfrom the biosensor to the reader.

It is thus an object of the invention to provide a biosensor and amethod that can be wirelessly operated and provides a more reliablesignal.

SUMMARY OF THE INVENTION

This object is achieved in a device as described in the openingparagraph characterised in that it comprises: a remote powertransmission element, a resonance circuit, said resonance circuitcomprising an resonance frequency determining sensor element or beingelectrically coupled to a resonance frequency determining sensorelement, wherein binding at the bonding sites effects a physicalproperty of the sensor element and thereby the resonance frequency, anda circuit for RF communication of an RF signal in dependence of theresonance frequency of the resonance circuit.

The object is achieved in a method as described characterised in that asensor device is used comprising a remote power transmission device, aresonance circuit comprising a resonance frequency determining sensorelement, or being electrically coupled to a resonance frequencydetermining sensor element, wherein binding at the bonding sites effectsa physical property of the sensor element and thereby the resonancefrequency, and a circuit for RF communication of an RF signal independence of the resonance frequency, the method comprising the stepsof:

Binding a target to binding sites of the sensor element

Sending light to the photodiode for powering the biosensor devicerecording the RF signal emitted by the circuit for RF communication.

In a device in accordance with the invention a physical property or anoutput of the sensor element determines a resonance frequency in theresonance circuit. A binding reaction of the analyte (or a particlecomprising the analyte, herein also called “the target”) to a bondingsite thus effects the resonance frequency (by effecting e.g. the L, theC, the R or the mass of the sensor). The change in the resonancefrequency is used as a signal. This signal is recorded in the method ofthe invention. The selectivity is not, or at least much less than in theknown devices, dependent on the intensity of the signal. Further more,the data conversion on the cartridge can be limited to a conversion ofe.g. a change in e.g. an L, C, R value to a frequency change, whichreduces the complexity of the device. Systematic deviations of theresonance frequency of the resonance circuit can be circumvented easily,if necessary, by measurement of a calibration sample at the same time.Further advantages are:

noise minimization can be effected easily by means of averaging over alonger time frame use can be made of impedance measurements, whichmeasurements are in any case more sensitive than fluorescentmeasurements.

A remote power transmission element is a device which is poweredremotely, it may e.g. be a photodiode, powered by light or a coil forpower transmission of RF power. A photodiode is preferred since itallows the provision of sufficient power (f.i. 0.5V per photodiode).Besides, in comparison with the use of a coil for power transmission, ithas the advantages that:

the necessary size of the photodiode is less than that of the inductor,thus minimizing surface of the chip, hence reducing costs for a powertransmission with an inductor a larger power source in the reader isnecessary.

the photodiode can be used as well for the transmission of signals tothe device of the invention. For this aim, the same or one or moreadditional photodiodes may be used. The signals can be transmitted bymodulation of the light. Alternatively, sensor elements of the devicemay be selectively activated through irradation with light from thephotodiodes.

In case a coil is used the for power transmission or RF power, theremote power transmission device is tuned to a frequency different fromthe signal RF frequency to avoid interference between the power signaland the measurement signal.

It is remarked that electrical biosensors and devices are known. Suchsensors measure a current (ΔI), voltage (ΔV), resistance (ΔR), orimpedance (ΔZ).

Some examples of electrical biosensors are: Amperometric, Resistive(e.g. magnetoresistance,) Potentiometric, Impedimetric (e.g.magneto-impedance, capacitive), Calorimetric, Field-effect devices,Redox reaction devices and other.

These electronic biosensors are always galvanically coupled to a readerstation.

There are several problems associated with galvanic contacts to a readerstation:

Galvanic contacts are unreliable. In a clinical environment, biosensorequipment is washed and sterilized, which deteriorates the galvaniccontacts and generates errors.

Galvanic contacts give ESD sensitivity.

Galvanic contacts require a relatively large pitch. This limits thenumber of contacts that can be made and unnecessarily increase the sizeand costs of the silicon chips.

Galvanic interfacing may require that conducting tracks are integratedin the cartridges, which complicates the device technology.

In the device in accordance with the invention the read-out is done viaan RF signal, i.e. remotely, which removes the problems associated withgalvanic couplings.

In respect of both types of known devices the sensitivity is greatlyincreased (by eliminating possible unreliabilities), while thecomplexity of the device is decreased.

In an embodiment the sensor element forms a part of the resonancecircuit. This provides for a relatively simple configuration.

In such embodiments the sensor element may form a capacitor or a coil ora resistor within the resonance circuit.

Alternatively the sensor element forms part of a voltage or currentsupplying circuit, coupled to the resonance circuit, wherein the voltageor current of the supplying circuit is dependent on a physical propertyof the sensor element, and the resonance frequency of the resonancecircuit is dependent on said voltage or current.

The invention further relates to a system of which the device of theinvention is part and in which the method of the invention can beexecuted.

Such is a system for detecting biomolecules in samples provided on abiosensor device, which system comprises the biosensor device and areader station comprising a power transmitting element for transmittingpower to the biosensor device and an antenna and a receiver forreceiving of signals to be wirelessly transmitted from the biosensordevice to the reader station with a transmitting frequency. It ischaracterized in that the device of the invention is present.Furthermore, the apparatus comprises or is connected to an analyser foranalysing the transmitting frequency of the signal of the biosensordevice or the change thereof with respect to a calibration frequency. Itis preferable that the system, and particularly the reader stationcomprises any means for processing said transmitting frequency and/orthe change thereof. Such means is for instance a microprocessor, withwhich the signal can be converted into a digital format. In additionthereto, a suitable memory may be present. In such a memory themeasuring data are preferably recorded with an identification number ofthe measured biosensor device. Furthermore, the reader station maycomprise means for transmitting the resulting data, particularly aconnection to a standard communication network, and/or means fordisplaying the results in the form of text or graphs. The invention alsorelates to a reader station that includes the means to do this.

These and other objects of the invention will be apparent from andelucidated with reference to the embodiments described hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic representation of a simple device of thisinvention.

FIG. 2 is a schematic representation of a layout of a device of thisinvention.

FIG. 3 schematically illustrates an electrical scheme for a device inaccordance with the invention.

FIG. 4 is similar to FIG. 3 but for the fact that the sensor element isby a capacitor.32.

FIG. 5 illustrates in more detail a part of FIG. 4.

FIG. 6 illustrates an embodiment in which the sensor element forms aresistive element.

FIG. 7 illustrates an embodiment in which the sensor element(s) form(s)a GMR magnetoresistive element in a Wheatstone bridge configuration forsupplying a voltage signal to a resonance circuit.

FIG. 8 schematically indicates a method in accordance with theinvention.

FIG. 9 illustrates a multiarray device in accordance with the invention.

FIG. 10 illustrates an embodiment of the invention in which the remotepower transmission element comprises a coil for receiving RF powerwhereby the remote power transmission element is arranged for receivingan RF frequency different from the resonance frequency.

In the different figures, the same reference numerals refer to the sameor analogous elements unless otherwise indicated.

DETAILED DESCRIPTION OF THE INVENTION

The present invention will be described with respect to a number ofembodiments and with reference to certain drawings but the invention isnot limited thereto.

FIG. 1 is a schematic representation of the device and method inaccordance with the invention. A biosensor cartridge 1 is provided witha photodiode 3 as a remote power transmission element. By shining light2 on the photodiode the device is provided with power. The light may bevisible light, UV or IR light, in an example the wavelength of the lightis 780 nm. The device further comprises an oscillator circuit comprisingin this example at least an amplifier 4 and a sensor element 5. Theresonance frequency (eigenfrequency) is dependent on the properties ofthe elements forming the resonance circuit, in particular e.g. thecapacitance, the inductance or the resistance of the sensor elementwithin the oscillator circuit. Also the mass could have an influence onthe oscillating frequency. The device 1 comprises a circuit (which maybe a separate circuit, the oscillator circuit itself or a larger entitycomprising the oscillator circuit) for RF communication. The RF signalis dependent on the oscillator frequency of the oscillator circuitcomprising the sensor element as one of its frequency determinativeelements. In an example the RF frequency is e.g. 720 mHz. A surface orpart of the sensor element 5 comprises bonding sites to which analytes 6a can bind. Generally labels or markers are used (beads 6 for instance)which bind to the binding sites 5 a if and only if they compriseanalytes 6 a. Binding of the beads results in a change in a physicalproperty of the sensor element (R,C,L, mass, surface wavecharacteristic) which in its turn changes the resonance frequency f ofthe resonance circuit, this can be done either directly, In case thesensor element forms a part of the resonance circuit per se as in thisschematically indicated figure or, as in other examples, by means of avoltage- or current-(or in general signal-) generating circuit coupledto the resonance circuit, wherein the voltage or current (or in generalsignal) of the voltage, current or signal producing circuit is dependenton a physical property of the sensor element, and in its turn determinesthe resonance frequency. The circuit for RF frequency emits a signaldependent on said change Δf (which signal could be a signal at theresonance frequency itself). This signal is emitted by the device 1 andreceived by receiver 7, which thus receives a signal comprisinginformation on the change Δf in the resonance frequency f. This receiver7 may have an analyser for analysing the change Δf or send the receivedsignal to an analyser for analysing the change Δf. Any material notbounded to the bonding sites will have no or hardly no influence on theresonance frequency.

In the known device a fluorescence signal from the fluorescent markersis measured, i.e. the beads 6 are fluorescent. To this end light isshone on the fluorescent markers which are supposed to be on a bindingsite. However, if a fluorescent marker is not present on a binding site,but still in the light path (e.g. if it is not carefully washed away),or if other substances in the sample interfere in the light path (e.g.light scattering or absorption) there is a chance that an erroneoussignal is produced. This contributes to the inaccuracy of themeasurement. This becomes especially a problem if in one device manydifferent analytes are to be measured. The fluorescent spectra offluorescent markers are usually relatively broad and as a consequence inan assay in which several analytes are used, great care must be takenthat cross-talk, i.e. a noise signal of a fluorescent signal of oneanalyte being present in the signal for the fluorescent marker for yetanother analyte, does not occur. Even if such care is taken this will goat the expense of the speed of measurement. In the present invention,one or more of these problem are greatly reduced because the signal Δfis produced within the resonance circuit and any remaining markersoutside the resonance circuit or not bounded on the surface will notinfluence the result. It is relatively easy to provide resonancecircuits with clearly distinguishable resonance frequencies, making itmore easy to distinguish one signal from another. This increases theaccuracy of the measurement, as well as the speed with which the signalsmay be measured and thus the test results may be obtained.

FIG. 2 schematically shows a more true to life example of a device asshown in FIG. 1. The device comprises a photo diode 3, an on-chipconductor 21 and a capacitor 22.

FIG. 3 schematically illustrates an electrical representation of adevice in accordance with the invention. The device comprises aphotodiode 3, drawn here as photo-current source I_(ph) in parallel withdiode D₀.

Schematically it is indicated that the oscillation circuit may comprisean inductance L (31), a capacitor C (32) and a resistive element R (33).The L, C and/or R value of these elements have an influence on theresonance frequency of the oscillator circuit. In different embodimentsof a device in accordance with the invention, the sensor element mayform a capacitor, a coil or a resistor within the resonance circuit. Inthis example it is schematically indicated that the sensor element formsan inductance L in the resonance circuit. Using magnetic beads 34 it ispossible to change the L value of the coil. In this embodiment thesensor element would e.g. be a foil coil, i.e. a flat coil on a surface.The bonding sites would be present at or near the surface of the coil.The presence of the magnetic beads 34 at the bonding site and thus nearthe coil changes the L value of the coil and thereby changes theresonance frequency of the resonance circuit. Some of the possible otherarrangements are schematically shown in FIGS. 4 to 8.

FIG. 4 is similar to FIG. 3. However, in this embodiment the sensorelement is not formed by a coil, but by a capacitor.32. In this examplethe beads 35 are for instance beads with a relatively high dielectricconstant. Binding at the binding sites will change the C value of thesensor element and thereby the resonance frequency of the oscillator.

FIG. 5 shows schematically details from FIG. 4. The resonance circuit isschematically indicated by the LC circuit and the amplifier A within thedotted-lined rectangle. The presence of the beads 35 in the capacitor Cchanges the capacitance of the capacitor and thereby the resonancefrequency. In this figure, as in other figures, an amplifier A isschematically shown, as resonance circuits often have an amplifyingpart.

FIG. 6 is similar to FIG. 3. However, in this embodiment the presence ofelectrically conductive beads at the resistance R changes the resistancevalue of said resistor and thereby the resonance frequency of theresonance circuit. A change in the resistance value of R will change thecurrent going into the resonance circuit and thereby change theresonance frequency of the resonance circuit.

FIG. 7 illustrates a variation on the scheme shown in FIG. 6. Thebiosensor comprises magnetoresistive detectors 71, 72 in a Wheatstonebridge configuration 70. The principles of magnetoresistive detectionare for instance described D. R. Baselt, “A biosensor based onmagnetoresistance technology”, Biosensors & Bioelectronics 13, 731-739(1998); in R. L. Edelstein et al., “The BARC biosensor applied to thedetection of biological warfare agents”, Biosensors & Bioelectronics 14,805 (2000); and in M. M. Miller et al., “A DNA array sensor utilizingmagnetic microbeads and magnetoelectronic detection”, Journal ofMagnetism and Magnetic Materials 225 (2001), pp. 138-144. Suitableimplementations are described in the non-prepublished applications EP01205092.8 (PHNL011000) and EP01205152.0 (PHNL010994). The resistancevalue R of one or more of the resistors is dependent on whether or notbinding has taken place. FIG. 7 illustrates a preferred embodiment inwhich the resistance of element 71 increase when binding takes place,indicated by the + sign in the figure, while for elements 72 theresistance decreases when binding takes place (indicated by the − sign).A Wheatstone bridge configuration is preferred since this allows forinstance temperature dependence of the R values to be automaticallycompensated, at least when the same type of resistive elements is usedin the bridge configuration. It is preferred to use thismagnetoresistive detection in combination with modulation of an externalmagnetic field. Such modulation allows the separation of magnetic andnon-magnetic contributions to the signal that is measured.

Magnetic labels are bonded to the sensor due to biochemicalinteractions. The labels are magnetised by an external magnetic field.The voltage from the Wheatstone bridge is dependent on the amount ofmagnetic labels located on the magnetoresistive sensors on the chip. Theresonance frequency of the on-chip LC oscillator is modulated by thisvoltage. The set-up of the GMR sensors is optimised towards maximalsignal at the output of amplifier 73. The on-chip inductor (see FIG. 2)may act as an antenna for the RF signal it generates. The voltage V isamplified by amplifier 73 and send to a varicap diode 75 in a resonancecircuit. In a variation on this scheme the output I from the bio-sensorsmodulates the frequency of the LC oscillator.

In yet a further embodiment of the invention the bio-sensors are locatedon the surface of an on-chip SAW/BAW (Surface Acoustic Wave/BulkAcoustic Wave) resonator which is part of a RF oscillator configuration.The bonded molecules will change the mass of the resonator surface andchange its resonance frequency. Since a SAW/BAW resonator does not emitRF spontaneously, an additional on-chip antenna can be required toenable RF transmission.

In a yet a further embodiment the bio-sensor signal is digitised andapplied as e.g. GFSK modulation to the RF oscillator. In this approachthe phase-noise of the RF oscillator will only influence thetransmission quality and not the quality of the bio-sensor signal.

FIG. 8 schematically indicates a method in accordance with the inventionand furthermore how a device in accordance with the invention may beused. In a vessel 80 a fluid having biomolecules is provided. To thisfluid a marker is provided with binds the biomolecules. Thereafter adevice (e.g. in the form of a chip) is provided having a sensor elementwith binding sites specific for the biomolecule. The biomolecules bindat the binding site at the sensor element. Light is shone on the chip,which emits in response an RF signal which is recorded by device 7. Inthis example the vessel is provided with only one chip, for simplicitysake. However, one of the great strengths of the devices and method inaccordance with the invention is that many different chip (having sensorelements for various biomolecules) may be provided simultaneously andrecorded simultaneously, as long as the resonance frequencies aredistinguishable. This allows the presence and/or concentrations of amultitude of biomolecules to be measured simultaneously and accurately,which is a great advantage, it also allows concentrations of suchbiomolecules to be monitored, i.e. measured as a function of timesimultaneously and accurately.

FIG. 9 schematically illustrates a more complex device in accordancewith the invention. In this device a large number of sub-devices 91,each in accordance with the invention is provided, at least some ofwhich are for different biomolecules and emitting differing RFfrequencies to a receiver 7. Each of the sub-devices has a fill opening92. This multiarray enables to check for the many different biomoculessimultaneously, accurately and fast.

It will be appreciated by persons skilled in the art that the presentinvention is not limited by what has been particularly shown anddescribed hereinabove. The invention resides in each and every novelcharacteristic feature and each and every combination of characteristicfeatures. Reference numerals in the claims do not limit their protectivescope. Use of the verb “to comprise” and its conjugations does notexclude the presence of elements other than those stated in the claims.Use of the article “a” or “an” preceding an element does not exclude thepresence of a plurality of such elements.

For instance, in the exemplary embodiments shown in FIGS. 1 to 9 theremote power transmission element comprises or is constituted by aphotodiode. FIG. 10 shows an example of a device and method inaccordance with the present invention in which the remote powertransmission element comprises a coil 101 forming a part of an RF powerreceiving element which is arranged to receive power via an RF powersignal at a frequency f1. This frequency differs from the RF frequencyf2 of the oscillator. By using different frequency the power signal doesnot interfere with the measurement signal.

In short the invention can be described as follows:

A device and method for measuring and or detecting the presence ofbiomolecules. The device comprises a resonance circuit arranged tooperate and emit a resonance frequency. The resonance circuit comprisesor is coupled to a sensor for detecting the binding of biomolecules tobinding sites. The binding of the biomolecules changes a physicalproperty of the sensor element, which in it's turn, either directly whenthe sensor element forms part of the resonance circuit, or via acoupling of the sensor element to the resonance circuit, the resonancefrequency. The change in the resonance frequency is detected. The devicecomprises a remote power transmission element, such as a photodiode orcoil, for providing power to the resonance circuit using light or RFradiation respectively.

1. A device (1) comprising a sensor element (5, 31, 32, 33, 71) havingbiomolecular binding sites (5 a) for a biomolecule (6 a), characterisedin that the device (1) comprises: a remote power transmission element(3, 101), a resonance circuit, said resonance circuit comprising anresonance frequency determining sensor element (5, 31, 32,) or beingelectrically coupled to a resonance frequency determining sensor element(33, 71), wherein binding at the binding sites (5 a) effects a physicalproperty (R, L, C, mass) of the sensor element (5, 31, 32, 33, 71) andthereby the resonance frequency (f), and a circuit for RF communicationof an RF signal (RF) in dependence of the resonance frequency of theresonance circuit.
 2. A device as claimed in claim 1, characterised inthat the remote power transmission element comprises a photodiode (3).3. A device as claimed in claim 1, characterised in that the remotepower transmission element comprises a coil (101) for receiving RF powerwhereby the remote power transmission element is arranged for receivingan RF frequency different from the resonance frequency.
 4. A device asclaimed in claim 1, characterised in that the sensor element (5, 31, 32)forms a part of the resonance frequency circuit.
 5. A device as claimedin claim 4, characterised in that the sensor element (33, 71) forms partof a voltage or current supplying circuit, coupled to the resonancecircuit, wherein the voltage (V) or current (I) of the supplying circuitis dependent on a physical property (R) of the sensor element, and theresonance frequency (f) of the resonance circuit is dependent on saidvoltage (V) or current (I).
 6. A device as claimed in claim 1 or 4,characterised in that the sensor element (71) is a GMR magnetoresistiveelement
 7. A device as claimed in claim 3 or 4, characterised in thatthe sensor elements are resistive elements provided in a bridgeconfiguration.
 8. A device as claimed in claim 2, characterised in thatthe sensors elements are located on the surface of an on-chip SAW/BAW(Surface Acoustic Wave/Bulk Acoustic Wave) resonator which is part ofthe oscillator circuit.
 9. A method for detecting biomolecules insamples using a device (1) comprising a sensor element (5, 31, 32, 33,71) having biomolecular binding sites (5 a) for a biomolecule,characterised in that a sensor device is used comprising a remote powertransmission element (3), a resonance circuit comprising an resonancefrequency determining sensor element (5, 31, 32), or being electricallycoupled to a resonance frequency determining sensor element (33, 71),wherein binding at the bonding sites effects a physical property of thesensor element (5, 31, 32, 33, 71) and thereby the resonance frequency,and a circuit for RF communication of an RF signal in dependence of theresonance frequency, the method comprising the steps of: a) Binding atarget to binding sites of the sensor element b) Remotely sending powerto the remote power transmission element for powering the biosensordevice c) recording the RF signal emitted by the circuit for RFcommunication.
 10. A method as claimed in claim 9, characterised in thatthe remote power transmission element comprises a photodiode (3) and instep b light (2) is shone on the photodiode.
 11. A method as claimed inclaim 9, characterised in that the remote transmission element comprisesa coil (101) for receiving RF power whereby the remote powertransmission element is arranged for receiving an RF frequency differentfrom the resonance frequency and in step b an RF frequency correspondingto the RF frequency of the remote power transmission element is emitted.12. A system for detecting biomolecules in samples provided on abiosensor device, which system comprises the biosensor device and areader station comprising a power transmitting element for transmittingpower to the biosensor device and an antenna and a receiver forreceiving of signals to be wirelessly transmitted from the biosensordevice to the reader station with a transmitting frequency,characterized in that: a device as claimed in any of the claims 1 to 8is present, the apparatus comprises or is connected to an analyser foranalysing the transmitting frequency of the signal of the biosensordevice or the change thereof with respect to a calibration frequency.13. A reader station comprising: a power transmitting element fortransmitting power to a biosensor device; an antenna and a receiver forreceiving of signals to be wirelessly transmitted from the biosensordevice to the reader station with a transmitting frequency, and ananalyser for analysing the transmitting frequency of the signal of thebiosensor device or the change thereof with respect to a calibrationfrequency.